I recently found out that Mazucanti CH et al had discovered that insulin was synthesized in the
choroid plexus within ependymal cells of the brain. I was very excited to learn this as a source of CNS derived insulin. It has long been thought that insulin may be synthesized in the brain but now we have proof for the first time. NOVEL findings. Important how does this finding deal with the insulin resistance that is thought to occur within the brain. Since I was studying the ependymal cells in the brain that lines the CSF side of the ventricles this was especially exciting to me.
These cells were also found not to be stimulated by glucose but to serotonin via their receptors on ependymal cells. There may other intraneuronal transmitters yet to found ?
Could the loss of Insulin signaling that is so closely tied to cognition in LOAD or aging be related to the dysfunction of ependymal cells that are also known to develop with aging ?
What would be the significance clinically in addition to scientifically in LOAD or the increased risk of LOAD in those with type 2 diabetes? Interestingly, this group did not find any evidence that ependymal cells synthesized or secreted amylin (IAAP) but they did not C-peptide in these regions where insulin was being produced. The beauty of this is that the secreted insulin could be rapidly carried to the median eminence of the CMO capillaries to signal the hypothalamic nuclei.
[Mazucanti CH, Liu QR, Lang D, Huang N, O’Connell JF, Camandola S, Egan JM. JCI Insight. 2019;4(23):e131682. https://doi.org/10.1172/jci.insight.131682
*Havrankova J, Roth J, Brownstein MJ. Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. ]
These findings are also important in that it has been known for some time that the circulating insulin levels had no effect on the brain’s insulin concentration (*).
[ *Havrankova J, Roth J, Brownstein MJ. Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents. J Clin Invest (1979) 64(2):636–4210.1172/JCI109504]
This topic is now open for the exchange of ideas and comments from all.
I think this topic is clinically relevant because soon the clinical trials of intranasal insulin will be available by Suzanne Craft et al and others who have been studying brain insulin for some time.
Melvin R Hayden, MD
University of Missouri School of Medicine
Columbia, Missouri USA
Significance of Insulin being synthesized and secreted in the brain
I apologize for the misspelling of words....!
Will this finding have implications in regards to how we think about centrally produced CNS insulin ? for example I left out a very important paper in regards to CNS insulin.. as follows by Banks et al: A must read-paper in this discussion.
[ Banks WA, Owen JB, Erickson MA. Insulin in the brain: there and back again. Pharmacol Ther. 2012;136(1):82–93. doi:10.1016/j.pharmthera.2012.07.006 ]
Thank you Dr. Elsayed I had hoped more would have contributed to this discussion.
Melvin Hayden
Article Insulin in the Brain: Its Pathophysiological Implications fo...
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